Compounds for the treatment or alleviation of edema, and methods for their use

Abstract

Isolated and substantially purified oligonucleotide compounds have been shown to be effective in reducing swelling and edema. Novel methods and substances are presented for the prevention, alleviation or treatment of edema of various aetiology.

The invention claimed is: 
     
       1. An oligonucleotide compound comprising a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, and SEQ ID NO 10. 
     
     
       2. The oligonucleotide compound according to  claim 1 , comprising a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 5, SEQ ID NO 6, and SEQ ID NO 7. 
     
     
       3. The oligonucleotide compound according to  claim 1 , comprising a SEQ ID NO 10. 
     
     
       4. The oligonucleotide compound according to  claim 1 , wherein the total length of the oligonucleotide is between about 12 and about 30 bases. 
     
     
       5. The oligonucleotide according to  claim 1 , wherein said oligonucleotide is chemically modified. 
     
     
       6. The oligonucleotide according to  claim 1 , wherein at least one nucleotide has a phosphate backbone modification. 
     
     
       7. The oligonucleotide according to  claim 6 , wherein at least one nucleotide has a phosphate backbone modification and said phosphate backbone modification is a phosphorothioate or phosphorodithioate modification. 
     
     
       8. A method for the prevention, treatment, and/or alleviation of edema in an individual, comprising administering to the individual an oligonucleotide compound comprising a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, and SEQ ID NO 10 in a dose effective to achieve one or several of modification of vascular permeability, inhibition of neutrophil migration/activation, inhibition or reduction of eosinophil migration, inhibition or reduction of leukocyte migration, and inhibition or reduction of lymphocyte migration. 
     
     
       9. The method according to  claim 8 , wherein the route of administration is buccal, oesophagal, gastric, mucosal, transdermal, subcutaneous, or intraperitoneal administration. 
     
     
       10. The method according to  claim 8 , wherein the mucosal administration is nasal administration, inhalation, ocular administration, rectal administration, oral administration, urogenital administration or vaginal administration. 
     
     
       11. The method according to  claim 8 , wherein the edema in the individual is linked to a disease selected from the group consisting of heart failure, liver cirrhosis, kidney diseases such as nephrotic syndrome, malnutrition, cancer, asthma, allergic rhinitis, acute lung injury, a lung disease involving the accumulation of exudate, COPD, ischemia, trauma and septic shock. 
     
     
       12. The method according to  claim 8 , wherein the oligonucleotide is administered in an amount of about 5 to about 500 μg per kg body weight. 
     
     
       13. The method according to  claim 12 , wherein the oligonucleotide is administered in an amount of about 10 to 100 μg per kg body weight. 
     
     
       14. The method of  claim 8 , wherein the oligonucleotide is administered prophylactically, before a procedure chosen from an invasive surgical procedure, radiation therapy, hormone treatment, graft surgery and transplantation. 
     
     
       15. The method of  claim 8 , wherein the oligonucleotide is administered prophylactically, before an expected exposure to an allergen. 
     
     
       16. The method of  claim 8 , wherein the oligonucleotide is administered in combination with anti-inflammatory medication. 
     
     
       17. The method according to  claim 8 , wherein the oligonucleotide compound comprises a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, and SEQ ID NO 7. 
     
     
       18. The method according to  claim 8 , wherein the oligonucleotide compound comprises a sequence selected from the group consisting of SEQ ID NO 8, SEQ ID NO 9, and SEQ ID NO 10. 
     
     
       19. The method of  claim 8 , wherein edema is defined as a disorder or dysfunction in interstitial fluid balance in an organ or tissue, linked to a condition selected from the group consisting of heart failure, liver cirrhosis, kidney diseases such as nephrotic syndrome, malnutrition, cancer, asthma, allergic rhinitis, COPD, ischemia, trauma and septic shock. 
     
     
       20. The method of  claim 8 , wherein said oligonucleotide is chemically modified. 
     
     
       21. The method of  claim 8 , wherein said oligonucleotide is chemically modified and at least one nucleotide has a phosphate backbone modification. 
     
     
       22. The method of  claim 8 , wherein said oligonucleotide is chemically modified through a phosphate backbone modification comprising a phosphorothioate or phosphorodithioate modification. 
     
     
       23. The oligonucleotide compound according to  claim 1 , comprising a sequence selected from the group consisting of SEQ ID NO 1 and SEQ ID NO 2. 
     
     
       24. An oligonucleotide compound consisting of a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, and SEQ ID NO 10. 
     
     
       25. The oligonucleotide compound according to  claim 24 , consisting of a sequence selected from the group consisting of SEQ ID NO 1 and SEQ ID NO 2. 
     
     
       26. The method according to  claim 8 , wherein the oligonucleotide compound comprises a sequence selected from the group consisting of SEQ ID NO 1 and SEQ ID NO 2. 
     
     
       27. The method according to  claim 8 , wherein the oligonucleotide compound consists of a sequence selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, and SEQ ID NO 10. 
     
     
       28. The method according to  claim 27 , wherein the oligonucleotide compound consists of a sequence selected from the group consisting of SEQ ID NO 1 and SEQ ID NO 2.